MeCP2-Dependent Transcriptional Repression Regulates Excitatory Neurotransmission

Erika D. Nelson, Ege T Kavalali, Lisa M Monteggia

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

Mutations in the transcriptional repressor, methyl-CpG binding protein 2 (MeCP2), result in a neurodevelopmental disorder called Rett Syndrome (RTT) [1-5]. Based on the neurological phenotypes observed in Rett patients, we examined the potential role of MeCP2 in synaptic function. We compared elementary properties of synaptic transmission between cultured hippocampal neurons from MeCP2 knockout and wild-type littermate control mice and found a decrease in the frequency of spontaneous excitatory synaptic transmission (mEPSCs) in neurons lacking MeCP2. We also detected a significant increase in the rate of short-term synaptic depression. To explore whether these functional effects can be attributed to MeCP2's role as a transcriptional silencer, we treated cultures with a drug that impairs histone deacetylation and examined spontaneous synaptic transmission. Treatment with this compound induced a similar decrease in mEPSC frequency in wild-type control cultures, but this decrease was occluded in MeCP2-deficient neurons. Interestingly, neither the loss of MeCP2 nor the drug treatment resulted in changes in mIPSC properties. Finally, by means of a lentivirus expressing Cre recombinase, we show that loss of MeCP2 function after neurodevelopment and synaptogenesis was sufficient to mimic the decrease in mEPSC frequency seen in constitutive MeCP2 KO neurons. Taken together, these results suggest a role for MeCP2 in control of excitatory presynaptic function through regulation of gene expression.

Original languageEnglish (US)
Pages (from-to)710-716
Number of pages7
JournalCurrent Biology
Volume16
Issue number7
DOIs
StatePublished - Apr 4 2006

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Methyl-CpG-Binding Protein 2
Synaptic Transmission
binding proteins
synaptic transmission
Neurons
neurons
Rett Syndrome
Drug therapy
Lentivirus
neurodevelopment
gene expression regulation
Gene Expression Regulation
Gene expression
histones
Pharmaceutical Preparations
Histones
drug therapy

Keywords

  • DNA

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

MeCP2-Dependent Transcriptional Repression Regulates Excitatory Neurotransmission. / Nelson, Erika D.; Kavalali, Ege T; Monteggia, Lisa M.

In: Current Biology, Vol. 16, No. 7, 04.04.2006, p. 710-716.

Research output: Contribution to journalArticle

Nelson, Erika D. ; Kavalali, Ege T ; Monteggia, Lisa M. / MeCP2-Dependent Transcriptional Repression Regulates Excitatory Neurotransmission. In: Current Biology. 2006 ; Vol. 16, No. 7. pp. 710-716.
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